Quercetin-mediated Mcl-1 and survivin downregulation restores TRAIL-induced apoptosis in non-Hodgkin's lymphoma B cells

Jacquemin, Guillaume; Granci, V.; Gallouet, Anne Sophie; Lalaoui, Najoua; Morlé, Aymeric; Iessi, Elisabetta; Morizot, Alexandre; Garrido, Carmen; Guillaudeux, Thierry; Micheau, Olivier

doi:10.3324/haematol.2011.046466

Cited by 77 publications

(58 citation statements)

References 41 publications

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“…6,7 In this context, current therapeutic approaches aim at combining TRAIL with conventional chemotherapy or targeted therapies to circumvent different resistances to TRAIL-induced apoptosis due to the presence of the antagonist receptors TRAIL-R3 (DcR1) and TRAIL-R4 (DcR2),the caspase-8 inhibitor c-FLIPor to a defect in the mitochondrial pathway. [8][9][10] Alternatively, mutagenesisor multimerization of TRAIL (or TRAIL derivatives)to mimic native membrane-bound TRAIL are explored to increase TRAIL efficacy. While 88 ng/mL TRAIL was required to kill 50 % of H1703 cells, the IC50 was reached with only8 ng/mL NPT, demonstrating that NPT action was largely superior than TRAIL one in inducing apoptosis of these cells.…”

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confidence: 99%

Nanovectorization of TRAIL with Single Wall Carbon Nanotubes Enhances Tumor Cell Killing

et al. 2015

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) is a member of the tumor necrosis factor (TNF) superfamily. This type II transmembrane protein is able to bound specifically to cancer cell receptors (i.e., TRAIL-R1 (or DR4) and TRAIL-R2 (or DR5)) and to induce apoptosis without being toxic for healthy cells. Because membrane-bound TRAIL induces stronger receptor aggregation and apoptosis than soluble TRAIL, we proposed here to vectorize TRAIL using single-walled carbon nanotubes (SWCNTs) to mimic membrane TRAIL. Owing to their exceptional and revolutional properties, carbon nanotubes, especially SWCNTs, are used in a wide range of physical or, now, medical applications. Indeed due to their high mechanical resistance, their high flexibility and their hydrophobicity, SWCNTs are known to rapidly diffuse in an aqueous medium such as blood, opening the way of development of new drug nanovectors (or nanocarriers). Our TRAIL-based SWCNTs nanovectors proved to be more efficient than TRAIL alone death receptors in triggering cancer cell killing. These NPTs increased TRAIL pro-apoptotic potential by nearly 20-fold in different Human tumor cell lines including colorectal, nonsmall cell lung cancer, or hepatocarcinomas. We provide thus a proof-of-concept that TRAIL nanovector derivatives based on SWCNT may be useful to future nanomedicine therapies.

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confidence: 99%

Nanovectorization of TRAIL with Single Wall Carbon Nanotubes Enhances Tumor Cell Killing

et al. 2015

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“…Our results were similar to the previously published data that demonstrated the resistance of C. albicans to 60 g/ml FCZ (3). The sensitization of human cancer cells by QC has been studied well in various carcinoma cell lines (36)(37)(38), but the sensitization of human fungal pathogens by QC has not been investigated. Upon combined treatment with QC and FCZ, NBC099 cells showed strongly en- …”

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confidence: 99%

Quercetin Sensitizes Fluconazole-Resistant Candida albicans To Induce Apoptotic Cell Death by Modulating Quorum Sensing

Singh

Upreti

Singh

et al. 2015

Antimicrob Agents Chemother

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dQuorum sensing (QS) regulates group behaviors of Candida albicans such as biofilm, hyphal growth, and virulence factors. The sesquiterpene alcohol farnesol, a QS molecule produced by C. albicans, is known to regulate the expression of virulence weapons of this fungus. Fluconazole (FCZ) is a broad-spectrum antifungal drug that is used for the treatment of C. albicans infections. While FCZ can be cytotoxic at high concentrations, our results show that at much lower concentrations, quercetin (QC), a dietary flavonoid isolated from an edible lichen (Usnea longissima), can be implemented as a sensitizing agent for FCZresistant C. albicans NBC099, enhancing the efficacy of FCZ. QC enhanced FCZ-mediated cell killing of NBC099 and also induced cell death. These experiments indicated that the combined application of both drugs was FCZ dose dependent rather than QC dose dependent. In addition, we found that QC strongly suppressed the production of virulence weapons-biofilm formation, hyphal development, phospholipase, proteinase, esterase, and hemolytic activity. Treatment with QC also increased FCZmediated cell death in NBC099 biofilms. Interestingly, we also found that QC enhances the anticandidal activity of FCZ by inducing apoptotic cell death. We have also established that this sensitization is reliant on the farnesol response generated by QC. Molecular docking studies also support this conclusion and suggest that QC can form hydrogen bonds with Gln969, Thr1105, Ser1108, Arg1109, Asn1110, and Gly1061 in the ATP binding pocket of adenylate cyclase. Thus, this QS-mediated combined sensitizer (QC)-anticandidal agent (FCZ) strategy may be a novel way to enhance the efficacy of FCZ-based therapy of C. albicans infections. Candidiasis is a prevalent fungal infection caused by species of the yeast genus Candida. There are more than Candida 20 species, the most common of which is Candida albicans. Candidiasis is the fourth most common cause of health care-associated bloodstream infections in India and the United States (1). This yeast normally lives on the skin and mucous membranes without causing infection. However, overgrowth of these microbes can cause superficial mycoses, invasive mucosal infections, and disseminated systemic disease, particularly in AIDS patients, transplant recipients, and other immunocompromised people (2, 3). It is well documented that the emergence of drug-resistant C. albicans is increasing at an alarming pace (4-6). Therefore, the need for effective anticandidal therapy is increasing, as the available drugs are still very restricted.Currently available therapies for candidiasis are based on antifungal drugs including azoles, echinocandins, and inhibitors of calcineurin, Hos2 deacetylase, and Hsp90 (7-10). Fluconazole (FCZ) is most widely used to treat candidiasis infections because of its high bioavailability and low toxicity (11-13). However, excessive and indiscriminate clinical use of FCZ has led to the emergence of multiple-drug-resistant (MDR) strains of C. albicans (5,14,15). Importantly, t...

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“…We then demonstrated that celecoxib potentiated TRAIL-induced apoptosis in lymphoma B cells, including TRAIL-resistant B-cell lines like RAJI and RL, which are much more resistant to cell death (ref. 32; Fig. 2A).…”

Section: Celecoxib Acts On B Cells Through Cox-2-independent Effects mentioning

confidence: 99%

COX-2–Independent Effects of Celecoxib Sensitize Lymphoma B Cells to TRAIL-Mediated Apoptosis

Gallouët

Travert

Bresson

et al. 2014

Clinical Cancer Research

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Purpose: Despite therapeutic advances, non-Hodgkin lymphomas (NHL) remain incurable. They form a group of neoplasms strongly dependent on their inflammatory microenvironment, which plays an important supportive role in tumor B-cell survival and in the resistance to antitumor immune response. New therapies must consider both tumor cells and their surrounding microenvironment Experimental Design: Stromal cells, derived from bone marrow or lymph nodes, and B cells from follicular lymphoma patients were cocultured or cultured alone with celecoxib treatment, a nonsteroidal anti-inflammatory drug, and/or TRAIL, a promising cytotoxic molecule for cancer therapy.Results: In this study, we show that follicular lymphoma stromal cells produce large amounts of PGE 2 . This production is abrogated after celecoxib treatment, targeting the COX-2 isoenzyme involved in PGE 2 synthesis. Furthermore, we demonstrate that celecoxib increases apoptosis in NHL B-cell lines and in primary follicular lymphoma B cells cocultured with stromal cells, but independently of the PGE 2 /COX-2 axis. Finally, celecoxib increases the apoptotic activity of TRAIL. We provide evidence that celecoxib affects proliferation and sensitizes NHL B-cell lines to apoptosis through COX-2-independent effects by slowing down the cell cycle and decreasing the expression of survival proteins, such as Mcl-1.Conclusions: These data suggest new potent strategies for NHL therapy combining drugs targeting both tumor B cells and survival signals provided by the tumor microenvironment.

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Quercetin-mediated Mcl-1 and survivin downregulation restores TRAIL-induced apoptosis in non-Hodgkin's lymphoma B cells

Cited by 77 publications

References 41 publications

Nanovectorization of TRAIL with Single Wall Carbon Nanotubes Enhances Tumor Cell Killing

Nanovectorization of TRAIL with Single Wall Carbon Nanotubes Enhances Tumor Cell Killing

Quercetin Sensitizes Fluconazole-Resistant Candida albicans To Induce Apoptotic Cell Death by Modulating Quorum Sensing

COX-2–Independent Effects of Celecoxib Sensitize Lymphoma B Cells to TRAIL-Mediated Apoptosis

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